The goal of this program is to understand the physiological function of a novel member of a class of ubiquitous proteins which is at the interface of two rapidly advancing areas: signal transduction and protein folding. Fpr3, the protein to be studied is a representative of the peptidylprolyl-cis,trans-isomerase (PPlase) family of enzymes which catalyses the cis-trans conversion of the peptide bond between proline and the preceding amino acid. PPlases are also the targets for a number of clinically used immunosuppressive drugs. When bound to the drug, certain PPlases inhibit the action of specific proteins required for the activation of T lymphocytes thereby preventing graft rejection during bone marrow and organ transplantation. Recent research has shown that in the absence of such drugs, PPlases are involved in the folding (or unfolding) and assembly (or disassembly) of proteins that participate in many diverse cellular processes ranging from stress response to transcriptional activation. Despite the ubiquitous distribution of the PPlase family, the physiological functions of these molecules remain largely unelucidated. Using the yeast Saccharomyces cerevisiae as a model system, I wish to establish the function of the PPlase family through the genetic and biochemical experiments that are proposed in this application . A series of genetic screens, including the two-hybrid screen will be performed to identify proteins that genetically interact with this PPlase and these interactions will also be tested through biochemical experiments. Interacting proteins will also be characterized through various biochemical approaches. The identification of Fpr3-interacting proteins should enhance our understanding of the pathways in which the PPlase family of proteins participates. In addition, it is possible that unique PPlase isotypes like Fpr3 may constitute new drug targets that could be exploited to develop novel chemotherapeutic strategies for clinical treatments other than immunosuppression.